PD-L1 Analyte ControlDR

Quality in Control

Product Codes: HCL019, HCL020 and HCL021

PD-L1_PI_v2

PD-L1 Analyte ControlDR 2

What is PD-L1? 3

The Role of PD-L1 in Cancer 3

PD-L1 Assessment 4

PD-L1 Product Details 5

PD-L1 Analyte Control Staining 6

HistoCyte Laboratories Ltd is based in the heart of the Newcastle University campus. Startedin 2014 by scientists with a combined experience of over 30 years in the development ofreagents for immunohistochemistry and in-situ hybridization. Collaborating withpathologists locally and globally, HistoCyte Laboratories Ltd is developing a range of costeffective products designed to help scientists to maintain and develop the quality of assayswithin their laboratory.

Contents

1.

PD-L1 Analyte ControlDR is part of the Dynamic Range ofHistoCyte Products. When a Dynamic Range of controlsdemonstrating the sensitivity of an assay is required, thePD-L1 Analyte ControlDR is ideal. This product contains fourcells of varying expression including a negative control cell.

PD-L1 Analyte ControlDR is available as pre-cut slides (2slide and 5 slides) and cell microarray blocks.

Format Product Code2 Slide HCL0195 Slide HCL020Block HCL021

PD-L1 Analyte ControlDR

2.

Programmed death ligand 1 (PD-L1) is a 40kD type 1transmembrane protein. Synonyms include:

• CD274

• B7 homolog 1 (B7-H1)

PD-L1 is a checkpoint regulator in immune cells1, it is expressedon immune or non-hematopoietic cells2. Expression of theprotein is seen during pregnancy where it has a role insupressing the immune system. PD-L1 induces an inhibitorysignal in activated T-cells and promotes T-cell apoptosis2.

What is PD-L1?

The Role of PD-L1 in Cancer

PD-L1 has been observed to be over expressed in a number of

different cancer types and is believed to be a potential means

by which the cancer cells can evade the immune system.

Overexpression of PD-L1 correlates with poor disease

outcomes3. The expression of PD-L1 within cancer is not

restricted to a single type of cancer and as such it has become

a target for anti-cancer drug development. Currently there are

a number of anti-PD-L1 clinical trials ongoing, focusing on the

following tumour types:

Lung cancer

Bladder cancer

Kidney cancer

Haematological cancer

Breast cancer

Colorectal cancer

Melanoma

Solid tumours

1. Dong H et al Nat Med 1999 5 1365-1369 2. Shi L et al J Hematol Oncol. 2013; 6: 74.3. Ohaegbulam K, et al Cell 2015 21, Issue 1, p24–33

3.

The diagram below (Figure 1.) illustrates the interaction

between the tumour cells and the immune system, whereby

the anti-PD-L1 antibody blocks the ability of the ligand to bind

with the PD-1 receptor. Thus preventing the inhibitory

feedback that would otherwise be stimulated.

Figure 1. The human leukocyte antigen (HLA) on the tumour cell presents tumour protein which is

detected through the T cell receptor (TCR). Upon recognising “tumour protein” the T cell initiates a

cytotoxicity event, which would otherwise be inhibited by the interaction between PD-L1 and PD-1

on the T cell.

PD-L1 Assessment

A number of different methods are used to measure PD-L1

expression, these include molecular methods such as:

• Real-time polymerase chain reaction (PCR) using

products such as TaqMan® gene expression assay from

ThermoFisher.

4.

• Fluorescence in situ hybridisation (FISH) probes for the

detection of PD-L1 DNA.

• Advanced Cell Diagnostics provide an RNAscope product

for the detection of PD-L1 mRNA.

A number of antibodies are available for the

immunohistochemical detection of PD-L1, these include clones:

• E1L3N (Cell Signalling Technology)

• SP263 (Ventana, Roche)

• SP142 (Spring Bioscience)

• 28-8 (Dako, Agilent).

• 22C3 (Dako, Agilent).

PD-L1 Product Details

The product consists of four different cell lines with PD-L1

expression levels of high, medium, low and negative. The

product was developed using the E1L3N PD-L1 antibody and

SP263. However, it has also been independently tested at

different laboratories using different PD-L1 antibodies with

different protocols. In all cases the HistoCyte PD-L1 control

provided the same high, medium, low and zero expression

range regardless of assay employed. All HistoCyte products are

designed to be suitable for FISH testing. All the cells are

amplified for PD-L1 except the negative cell line.

5.

Cell Signalling Technologies Clone: SP263Performed on the Roche Ventana Benchmark UltraTM

PD-L1 Analyte ControlDR stainingT

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High expression: Strong staining in majority of cells.

Medium expression: Convincing staining in majority of cells. Some strong staining.

Low expression: Faint staining in majority of cells. Occasional strong staining.

Negative expression: Absence of any genuine staining.

6.

Additional assessment: mRNA levels by QT-PCR correlated to the IHC results.

Also Available from HistoCyte Laboratories Ltd

For more information email: info@histocyte.com

For orders email: sales@histocyte.com

Telephone: +44 (0) 191 603 1007

For your local distributor please visit www.histocyte.com

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